REF2HCT: Haploidentical Bone Marrow Transplant for Leukemia and Lymphoma

Provision of TCRγδ T Cells and Memory T Cells plus Selected Use of Blinatumomab in Naïve T-cell Depleted Haploidentical Donor Hematopoietic Cell Transplantation for Hematologic Malignancies Relapsed or Refractory despite Prior Transplantation

Categories:

Leukemia / Lymphoma

Bone Marrow Transplant

Phase I/II

Diseases Treated:

Eligibility Overview:

  • 21 years old and younger
  • Diagnosed with one of the following that has come back or did not improve after bone marrow transplant
    • Acute lymphoblastic leukemia (ALL)
    • Acute myeloid leukemia
    • Myeloid sarcoma
    • Chronic myeloid leukemia (CML)
    • Juvenile myelomonocytic leukemia (JMML)
    • Myelodysplastic syndrome (MDS)
    • Non-Hodgkin lymphoma (NHL)
  • Has a family member who is a suitable stem cell donor
  1. Brief Summary

    Recurrent disease is the most common cause of death in children with hematologic malignancies. Patients who fail dose-intense conventional chemotherapeutic regimens and then relapse after allogeneic hematopoietic cell transplant (HCT) have a poor prognosis and are rarely suitable candidates for conventional HCT. Patients who relapse after allogeneic HCT are often in poor clinical condition and are frequently ineligible to receive an equally intense second transplant.

    New treatments are desperately needed for these patients. Therapies that reduce regimen-related toxicity and relapse while promoting rapid immune reconstitution free of serious GVHD will likely improve disease-free survival and quality of life.

    Many patients who need a repeat allogeneic HCT have already failed after an HLA-matched sibling donor HCT or lack an HLA-matched sibling and are not able to wait for an unrelated donor. However, nearly all patients have a readily available mismatched family member (haploidentical) donor.

    St. Jude researchers have found that selective depletion of CD45RA+ cells provides efficient depletion of B cells and acute GVHD inducing naïve T cells, while preserving hematopoietic progenitor cells and memory T cells. In addition to more rapid recovery of protection against infection, adoptively transferred memory T cells may provide anti-rejection and anti-leukemia effects. Similarly, there is evidence in the literature that TCRγδ T cells likewise may facilitate engraftment and have anti-leukemia effects. This study will evaluate the safety and efficacy of selective naïve T-cell depleted haploidentical HCT following a reduced intensity conditioning regimen that avoids radiation in this patient population. Patients with a CD19+ malignancy may also receive blinatumomab, which may work with donor memory T cells to kill any residual leukemia.

    Primary Objective

    • To estimate engraftment by day +42 post-transplant in patients who receive TCRαβ-depleted and CD45RA-depleted haploidentical donor progenitor cell transplantation following reduced intensity conditioning regimen without radiation

    Secondary Objectives

    • To assess the safety and feasibility of the addition of Blinatumomab in the early post-engraftment period in patients with CD19+ malignancy
    • To estimate the incidence of malignant relapse, event-free survival and overall survival at one year post-transplantation
    • To estimate incidence and severity of acute and chronic (GVHD)
    • To estimate the rate of transplant-related mortality in the first 100 days after transplantation

    Eligibility Criteria

    Inclusion criteria for transplant recipient include:

    • 21 years old and younger
    • Diagnosed with one of the following hematologic malignancies that has relapsed or remains refractory after prior allogeneic hematopoietic cell transplant:
      • Acute lymphoblastic leukemia (ALL)
      • Acute myeloid leukemia
      • Myeloid sarcoma
      • Chronic myeloid leukemia (CML)
      • Juvenile myelomonocytic leukemia (JMML)
      • Myelodysplastic syndrome (MDS)
      • Non-Hodgkin lymphoma (NHL)
    • Has a suitable single haplotype matched (≥ 3 of 6) family member donor

    Study Sites

    St. Jude Children’s Research Hospital
    Memphis, Tennessee

  2. About this Study

    Cancers like leukemia and lymphoma are often treated with chemotherapy. Sometimes, the cancer comes back, or relapses, after treatment. In other cases, the cancer does not improve after treatment.

    Doctors may treat tough cancers like these with a bone marrow transplant, also called a hematopoietic (blood) cell transplant. The procedure begins with chemotherapy (strong cancer medicine) to kill the patient’s bone marrow and make room for the transplanted cells. Next, doctors remove cells from a donor and inject them into the patient. These donor blood cells grow in the patient and make new blood cells to fight the cancer.

    The best donor for this type of transplant is a brother or sister who matches the patient’s immune type. If the patient does not have a brother or sister who is a suitable donor, another donor may be used. Other donors may include someone who is not related to the patient or a family member who is only a partial match.

    This clinical trial will treat patients whose cancer has come back or worsened despite having a previous bone marrow transplant. In this St. Jude study, doctors will perform a new bone marrow transplant using donor cells from a family member who is a partial match for the patient’s immune type. This type of transplant is called a haploidentical transplant.

    Purpose of this Clinical Trial

    The main goal of this study is to learn about the good and bad effects of transplanting blood cells donated by a family member to children and young adults with cancer that has come back or did not improve after a previous bone marrow transplant.

    Eligibility Overview

    • 21 years old and younger
    • Diagnosed with one of the following that has come back after a previous bone marrow transplant  or did not improve after bone marrow transplant
      • Acute lymphoblastic leukemia (ALL)
      • Acute myeloid leukemia
      • Myeloid sarcoma
      • Chronic myeloid leukemia (CML)
      • Juvenile myelomonocytic leukemia (JMML)
      • Myelodysplastic syndrome (MDS)
      • Non-Hodgkin lymphoma (NHL)
    • Has a family member who is a suitable stem cell donor
  3. REF2HCT Quick View
    Sponsors St. Jude Children’s Research Hospital
    ClinicalTrials.gov identifier NCT02790515
    Trial Start Date June 2016
    Estimated Enrollment 18
    Study Type Interventional
    Study Phase II
    Conditions Leukemia, Non-Hodgkin Lymphoma, Myeloid Sarcoma, Myelodysplastic Syndrome
    Ages 21 years old and younger
    Principal investigator Brandon Triplett, MD
    Study sites St. Jude Children’s Research Hospital 
    For a consultation or to discuss REF2HTC St. Jude Physician/Patient Referral Office
    1-888-226-4343
    referralinfo@stjude.org

Contact

Brandon Triplett, MD

St. Jude Children’s Research Hospital
262 Danny Thomas Place
Memphis, TN 38105  USA
Voice: 1-888-226-4343 or 901-595-4055
24-Hour Emergency Access Pager: 1-800-349-4334
Email: referralinfo@stjude.org

The above information is intended to provide only a basic description about a research protocol that may be currently active at St. Jude. The details made available here may not be the most up-to-date information on protocols used by St. Jude. To receive full details about a protocol and its status and or use at St. Jude, a physician must contact St. Jude directly.